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ID PMID Title PublicationDate abstract
34523302 Does dehydroepiandrosterone sulfate have a role in COVID-19 prognosis and treatment? 2021 Sep 13 The pathophysiology of COVID comprises an exaggerated pro-inflammatory response. Hypothalamic-pituitary-adrenal (HPA) axis has a crucial role in various inflammatory conditions and modulated immunological response. Limited evidence is available regarding the incidence and the effect of HPA dysfunction in COVID-19. Although the cortisol levels have only been estimated in a few studies, the dehydroepiandrosterone sulfate (DHEAS) release from the adrenal gland has not been explored yet. In this mini review, the authors discuss the role of dehydroepiandrosterone (DHEA) and DHEAS in the acute stress response and immunological modulation. Various effects of DHEAS have been demonstrated in different diseases. The specific inhibitory effect of DHEA on interleukin 6 (IL-6) could be of paramount importance in COVID-19. Further, DHEA supplementation has already been proposed in inflammatory conditions, like rheumatoid arthritis. DHEAS levels in COVID-19 may help to understand the HPA axis dysfunction as well as the possibility of repurposing DHEA as a drug for mitigating the pro-inflammatory COVID-19.
34489018 Biosynthesis of actarit using engineered Escherichia coli. 2021 Oct Actarit is widely regarded as a safe and effective drug for the treatment of rheumatoid arthritis. There is no report on the bioproductin of actarit so far. In this study, we demonstrated for the first time the development of an artificial actarit biosynthetic pathway in Escherichia coli. First, 4-aminophenylacetic acid is selected as precursor substrates for the production of actarit. Second, an N-acetyltransferase that can efficiently catalyse the esterification of acetyl-CoA and 4-aminophenylacetic acid to form actarit was discovered. Subsequently, an engineered E. coli that allows production of actarit from simple carbon sources was established. Finally, we further increased the production of actarit to 206 ± 16.9 mg/L by overexpression of shikimate dehydrogenase ydiB and shikimate kinase aroK.
33604209 Obesity and Mechanical Thrombectomy. 2021 Jan 13 Background Obesity has been shown to have a positive mortality benefit in patients undergoing percutaneous coronary intervention, dialysis, those with rheumatoid arthritis, chronic obstructive pulmonary disease, and various wasting diseases. Studies for this mortality benefit in ischemic stroke patients are conflicting, and it has not been well studied in mechanical thrombectomy patients. We sought to determine the impact of obesity on outcomes of mechanical thrombectomy patients. Methodology We used a large global health research network to gather clinical data extracted from the electronic medical records of ischemic stroke patients who underwent mechanical thrombectomy, and then stratified these patients into obese and non-obese cohorts. The primary endpoint was mortality. Results After propensity score matching, obese patients who underwent mechanical thrombectomy had decreased mortality (p = 0.0033, odds ratio = 0.81, 95% confidence interval = 0.704,0.932) compared to non-obese patients. No statistically significant difference was shown between these two cohorts for the outcomes of ventilator dependence, hemicraniectomy, or post-procedure intracerebral hemorrhage. Conclusion Despite increasing risk of ischemic stroke, obese patients who undergo mechanical thrombectomy have decreased mortality rates compared to their non-obese counterparts.
33552242 Human endogenous retroviruses in cancer: Expression, regulation and function. 2021 Feb Human endogenous retroviruses (HERVs) are the remnants of ancient retroviruses that infected human germline cells and became integrated into the human genome millions of years ago. Although most of these sequences are incomplete and silent, several potential pathological roles of HERVs have been observed in numerous diseases, such as multiple sclerosis and rheumatoid arthritis, and especially cancer, including breast cancer and pancreatic carcinoma. The present review investigates the expression signatures and complex regulatory mechanisms of HERVs in cancer. The long terminal repeats-driven transcriptional initiation of HERVs are regulated by transcription factors (such as Sp3) and epigenetic modifications (such as DNA methylation), and are influenced by environmental factors (such as ultraviolet radiation). In addition, this review focuses on the dual opposing effects of HERVs in cancer. HERVs can suppress cancer via immune activation; however, they can also promote cancer. HERV env gene serves a prime role in promoting carcinogenesis in certain malignant tumors, including breast cancer, pancreatic cancer, germ cell tumors, leukemia and Kaposi's sarcoma. Also, HERV ENV proteins can promote cancer via immune suppression. Targeting ENV proteins is a potential future antitumor treatment modality.
34928185 The role of PCSK9 in inflammation, immunity, and autoimmune diseases. 2022 Jan INTRODUCTION: Statins have pleiotropic effects, being both anti-inflammatory and immunomodulatory. Proprotein convertase subtilisin kexin 9 (PCSK9) targets the low-density lipoprotein receptor (LDLR), which increases LDL levels due to the lower expression of LDLR. AREAS COVERED: Inhibition of PCSK9 by the use of antibodies represents a novel principle to lower LDL levels. LDL may have other properties than being a cholesterol carrier but is well established as a risk factor for cardiovascular disease and atherosclerosis. In atherosclerosis, the plaques are characterized by activated T cells and dendritic cells (DCs), dead cells, and OxLDL. The latter may be an important cause of the inflammation typical of atherosclerosis, by promoting a proinflammatory immune activation. This is inhibited by PCSK9 inhibition, and an anti-inflammatory type of immune activation is induced. OxLDL is raised in systemic lupus erythematosus (SLE), where both CVD and atherosclerosis are much increased compared to the general population. PCSK9 is reported to be associated with disease activity and complications in SLE. Also in other rheumatoid arthritis, PCSK9 may play a role. EXPERT OPINION: PCSK9 has pleiotropic effects, being implicated in inflammation and immunity. Inhibition of PCSK9 is therefore interesting to study further as a potential therapy against inflammation and autoimmunity.
34422057 Tocilizumab Effect on Lipid Profile in Correlation to Cardiovascular Events: A Retrospecti 2021 OBJECTIVE: To study the effect of tocilizumab initiation on the lipid profile, in correlation to a composite of any cardiovascular events. METHODS: A retrospective cohort study, using data from the King Faisal Specialist Hospital & Research Centre database, from January 2014 to December 2019. Patients with rheumatoid arthritis or juvenile idiopathic arthritis who were ≥18 years old, initiated either on tocilizumab or other biologic treatment (anti-TNFs or Rituximab), were included, with a follow-up interval duration at a minimum of 6-12 months up to 3-5 years. Any patient with established cardiovascular disease or aged <18 were excluded. RESULTS: Only one cardiovascular mortality was reported in the tocilizumab group. Fifty percent of patients reached high cholesterol levels ≥ 5.2 mmol/L and LDL ≥ 3.37 mmol/L in the tocilizumab group at 36 months in a shorter time period compared to controls (60 months), P 0.001. There were no significant differences between groups for statin use (27% vs. 28%) However, there was a significantly higher mean dose of atorvastatin in the tocilizumab group compared to controls (20.6 mg vs. 16.6 mg, P 0.03). CONCLUSION: There was a lack of evidence of increased cardiovascular risk in correlation to hyperlipidemia secondary to tocilizumab treatment.
34234420 Usability of the Certolizumab Pegol Auto-Injection Device in Australian Patients with Chro 2021 PURPOSE: To determine the usability of the ergonomically designed certolizumab pegol pre-filled pen (CZP PFP) in Australian patients with active ankylosing spondylitis, active psoriatic arthritis or moderate-to-severe rheumatoid arthritis. PATIENTS AND METHODS: CZP-naive patients were recruited from six clinical centers in Australia between November 2018 and May 2019. Patients and healthcare professionals (HCPs) reviewed training materials and completed pre-injection surveys; patients then self-administered ≥1 injection with the CZP PFP during each of three visits. Patients and HCPs then completed post-injection surveys. Some survey questions were adapted from the self-injection assessment questionnaire (SIAQ(v2.0)). RESULTS: Seventy patients participated (65 completed 3 visits); 33 were biologic-experienced. All patients agreed that training materials were informative; 94% found them easy to understand. Pre-injection, 89% of patients reported little or no anxiety about having injections; 67% (79% in biologic-experienced) were very confident about self-injecting the correct dose with the PFP. Ninety percent of patients were satisfied/very satisfied with their first experience with the CZP PFP; those with pre-injection anxiety reported lower satisfaction (43% vs 79% "very satisfied"). Confidence and satisfaction increased as visits progressed (for Visit 3 vs Visit 2: 69% vs 56% "very convenient"; 75% vs 67% "very confident"; 71% vs 57% "very satisfied"). All HCPs were confident in their patients' competence to self-inject and thought all patients had overall positive experiences. CONCLUSION: Australian patients with chronic rheumatic disease reported high levels of confidence and satisfaction following initial use of the CZP PFP. The availability of devices with patient-centered design innovations may help overcome barriers to self-injection for improved adherence/outcomes.
34060251 Environmental Air Pollution Is a Predictor of Poor Response to Biological Drugs in Chronic 2021 Jul BACKGROUND: There is increasing evidence that environmental air pollution is associated with the development of chronic inflammatory arthritides (CIA). The role of air pollutants on the biological treatment (biological disease-modifying antirheumatic drugs [bDMARDs]) response of CIA is still unclear. METHODS: We retrieved longitudinal data on patients affected by CIA on biological therapies and on the daily concentration of air pollutants in the Verona area. We designed a case-crossover study to compare the exposure to pollutants in the 60-day period preceding a drug switch or swap due to disease progression referent to the 60-day period preceding a visit with stable treatment for at least 6 months. RESULTS: A total of 1257 patients with CIA (863 with rheumatoid arthritis, 256 with psoriatic arthritis, and 138 with ankylosing spondylitis) with 5454 follow-up visits were included in the study (median follow-up 2.09 years [interquartile range: 0.82-2.58 years]). A total of 282 patients were included in the case-crossover study. We retrieved 13 636 daily air pollution records. We found that air pollutants' concentrations were higher in the 60-day period before a failure of bDMARD response and prior to a switch or swap compared with the period preceding a visit with stable bDMARD therapy for at least 6 months. CONCLUSION: We found that environmental air pollution was a determinant of poor response to bDMARDs in a cohort of patients with CIA followed over a 5-year period. An intervention aimed at decreasing fossil combustion emissions might have beneficial effects on biologic persistence rates of patients with CIA and economic expenditures related to switches and swaps.
33606503 Prioritizing Pain-Associated Targets with Machine Learning. 2021 May 11 While hundreds of genes have been associated with pain, much of the molecular mechanisms of pain remain unknown. As a result, current analgesics are limited to few clinically validated targets. Here, we trained a machine learning (ML) ensemble model to predict new targets for 17 categories of pain. The model utilizes features from transcriptomics, proteomics, and gene ontology to prioritize targets for modulating pain. We focused on identifying novel G-protein-coupled receptors (GPCRs), ion channels, and protein kinases because these proteins represent the most successful drug target families. The performance of the model to predict novel pain targets is 0.839 on average based on AUROC, while the predictions for arthritis had the highest accuracy (AUROC = 0.929). The model predicts hundreds of novel targets for pain; for example, GPR132 and GPR109B are highly ranked GPCRs for rheumatoid arthritis. Overall, gene-pain association predictions cluster into three groups that are enriched for cytokine, calcium, and GABA-related cell signaling pathways. These predictions can serve as a foundation for future experimental exploration to advance the development of safer and more effective analgesics.
34561652 Detection of microvascular changes in systemic sclerosis and other rheumatic diseases. 2021 Nov Morphological and functional analysis of the microcirculation are objective outcome measures that are recommended for use in the presence of clinical signs of altered peripheral blood flow (such as Raynaud phenomenon), which can occur in systemic sclerosis (SSc) and other autoimmune rheumatic diseases. Several advanced non-invasive tools are available for monitoring the microcirculation, including nailfold videocapillaroscopy, which is the best-studied and most commonly used method for distinguishing and quantifying microvascular morphological alterations in SSc. Nailfold videocapillaroscopy can also be used alongside laser Doppler techniques to assist in the early diagnosis and follow-up of patients with dermatomyositis or mixed connective tissue disease. Power Doppler ultrasonography, which has been used for many years to evaluate the vascularity of synovial tissue in rheumatoid arthritis, is another promising tool for the analysis of skin and nailbed capillary perfusion in other autoimmune rheumatic diseases. Other emerging methods include raster-scanning optoacoustic mesoscopy, which offers non-invasive high-resolution 3D visualization of capillaries and has been tested in psoriatic arthritis and SSc. The principle functions and operative characteristics of several non-invasive tools for analysing microvascular changes are outlined in this Review, and the clinical roles of validated or tested imaging methods are discussed for autoimmune rheumatic diseases.
35478563 Traditional uses, phytochemistry, pharmacology, and toxicology of Pterocephalus hookeri (C 2021 Aug 23 Pterocephalus hookeri (C. B. Clarke) Höeck is a member of the Dipsacaceae family and has been used in traditional Tibetan medicine for thousands of years. P. hookeri clears heat, detoxifies, stops dysentery, eliminates distemper, dispels wind, and relieves stagnation and is mainly prescribed for heat syndrome, dysentery, arthritis, and plague. Approximately 93 chemical compounds have been isolated and identified from P. hookeri, including iridoid glycosides, lignan and triterpenoids. Meanwhile, modern pharmacological studies have shown that P. hookeri has anti-inflammatory, anti-rheumatoid arthritis, analgesic, anticancer, and neuroprotection activities. However, studies on the in vivo pharmacokinetics and mechanism of action, discovery of quality markers, and qualitative and quantitative analysis are still insufficient. Hence, this paper provides a comprehensive review of the ethnic medicine, phytochemistry, pharmacology, and toxicology of P. hookeri to increase the understanding of the medicinal value of P. hookeri.
35415579 Retrospective Data Collection of Distal Interphalangeal Joint Fusion With X Fuse Superelas 2021 Nov PURPOSE: Arthrodesis of the distal interphalangeal joint of the fingers and interphalangeal joint of the thumb is a common procedure for multiple diagnoses. The purpose of this study was to evaluate fusion rates and complications in patients who have been previously implanted with an X Fuse superelastic implant (Stryker). METHODS: All patients who underwent distal interphalangeal and/or thumb interphalangeal joint fusion between June 2013 and May 2019 were included by the senior author. A chart review was used to note demographics; hand dominance; and medical and surgical history, including complications, comorbidities, clinical recovery, absence of pain, and functional use. Pre- and postoperative radiographs were evaluated for angular deformity, postoperative correction of that deformity, boney consolidation, and tine cutout. RESULTS: Fifty-three patients (60 fingers; 43 women and 10 men) with a mean age of 62.6 years were included. The surgical diagnoses included hereditary osteoarthritis in 45 patients, rheumatoid arthritis in 4, psoriatic arthritis in 1, swan or mallet fingers in 5, ulnar motor loss instability in 2, and trauma or a fracture in 3. For X Fuse, an implant angle of 0° was used in 51 cases, whereas 15° was used in 9 cases. Bone consolidation was observed in all but 1 patient at an average time of 9.7 weeks (range 4.1-17.6 weeks). The X Fuse superelastic implant in small bones demonstrated minimal complications and a 98% (59/60) fusion rate. CONCLUSIONS: The X Fuse superelastic implant produced a reliable fusion, with no implant prominence and a 1.7% (1/60) rate of hardware removal. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
34353999 Janus Kinase inhibitors for the treatment of hospitalized patients with COVID-19. 2021 Oct 1 PURPOSE OF REVIEW: Janus Kinase (JAK) inhibitors have been successfully utilized in the clinical treatment of several rheumatologic (e.g. rheumatoid arthritis) and inflammatory diseases (e.g. hemophagocytic lymphohistiocytosis). Based on the growing evidence that moderate and severe COVID-19 infections are associated with a dysregulated inflammatory state, this class of medications has been repurposed as a potential therapy for COVID-19, an infection caused by Severe Acute Respiratory Syndrome Coronavirus 2. RECENT FINDINGS: Three JAK inhibitors have been evaluated in human studies of COVID-19: Baricitinib, Tofacitinib, and Ruxolitinib. Most published studies are observational, but three randomized placebo-controlled double-blind trials have been completed: two large trials (N = 2,558 patients) with baricitinb demonstrated significant faster improvement in clinical status and reduction in the recovery time, as well as, significant reduction in the progression to invasive mechanical ventilation and mortality. One smaller randomized trial (N = 289) involving tofacitinib showed significant reduction in the progression to invasive ventilation or death. Notably, these three randomized placebo-controlled trials with close to 3,000 patients did not reveal any safety concerns associated with JAK inhibitors in terms of secondary infections or venous thromboembolism. Based on this high-quality evidence, both the Infectious Diseases Society of America and the National Institutes of Health guidelines recommend using baricitinib as part of the treatment approach for hospitalized patients with COVID-19. SUMMARY: JAK inhibitors are novel treatment agents in the field of infectious diseases. One JAK inhibitor, baricitinib has demonstrated significant clinical and survival benefits in hospitalized patients with COVID-19 in phase III randomized placebo-controlled trials. Baricitinib is already recommended for clinical practice by multiple guidelines.
34042325 Is There a Place for Chimeric Antigen Receptor-T Cells in the Treatment of Chronic Autoimm 2021 Nov Chimeric antigen receptor-T (CAR-T) cell therapy is based on specific targeting of tumor antigens, leading to lysis and destruction of tumor cells. The high potency of CAR-T cells in the management of B cell malignancies has been demonstrated. Following the success of this therapeutic strategy, new CAR-T cell-derived constructs that have the ability to eradicate pathogenic B cells or restore tolerance have been developed. The present review discusses how the knowledge and technology generated by the use of CAR-T cells may be translated and integrated into ongoing therapeutic strategies for autoimmune rheumatic diseases. To this end, we describe the details of CAR-T cell technology, as well as the meaningful achievements attained with the use of CAR-T cells in onco-hematology. In addition, we review the preliminary data obtained with CAR-T cells and their derivative constructs in experimental models of autoimmune diseases. Finally, we focus on how CAR-T cell engineering interferes with the pathogenesis of 3 chronic autoimmune rheumatic diseases-rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis-and discuss whether these constructs might yield greater efficacy and be associated with fewer adverse events compared to current treatment strategies.
33339986 Rheumatic disease and COVID-19: epidemiology and outcomes. 2021 Feb Since the outset of the COVID-19 pandemic, numerous risk factors for severe disease have been identified. Whether patients with rheumatic diseases, especially those receiving DMARDs, are at an increased risk of SARS-CoV-2 infection or severe COVID-19 disease remains unclear, although epidemiological studies are providing some insight.
32887541 Tablet Formulation of a Synthesized Celecoxib Potassium Salt and Development of a Validate 2021 BACKGROUND: Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) and cyclooxygenase-2 (COX-2) inhibitor. It is used for the treatment of rheumatoid arthritis, osteoarthritis, juvenile arthritis, and acute pain. Celecoxib has low systemic bioavailability due to its low water solubility. This study aimed to improve water solubility and dissolution profile by synthesizing a suitable celecoxib potassium salt (celecoxib-K salt). METHODS: Four celecoxib salts were synthesized, and the solubility of these four salts was determined. Celecoxib- K monohydrate salt was chosen for tablet formulation. A simple and feasible reversed-phase high-performance liquid chromatography (HPLC) method was developed for the analysis of the formulated tablet and then validated according to international guidelines. The dissolution profile, shelf life, and accelerated stability studies on the formulated tablet were conducted. RESULTS: Celecoxib-K monohydrate salt exhibited increased water solubility by more than 140-folds (0.464 mg/ml) compared with celecoxib. The in vitro dissolution profile of the formulated celecoxib-K salt tablet was totally dissolved after 10 min. The developed analytical HPLC method was a reliable and valid method with good linearity, accuracy, and precision. Moreover, it was sensitive, and the limit of detection and quantification (LOD and LOQ) were 0.001 and 0.1 mg/L, respectively. The formulated celecoxib-K monohydrate salt tablet was stable under room temperature and accelerated condition for 60 days. CONCLUSION: The potassium salt of celecoxib was highly increased, and the formulated tablet of celecoxib-K salt exhibited a good dissolution profile in the water. In addition, the developed HPLC method was valid and reliable for the analysis and quantification of the formulated tablet. The formulated tablet was stable both at room temperature and under stress conditions.
33094664 LncRNAs in adaptive immunity: role in physiological and pathological conditions. 2021 May The adaptive immune system is responsible for generating immunological response and immunological memory. Regulation of adaptive immunity including B cell and T cell biology was mainly understood from the protein and microRNA perspective. However, long non-coding RNAs (lncRNAs) are an emerging class of non-coding RNAs (ncRNAs) that influence key factors in lymphocyte biology such as NOTCH, PAX5, MYC and EZH2. LncRNAs were described to modulate lymphocyte activation by regulating pathways such as NFAT, NFκB, MYC, interferon and TCR/BCR signalling (NRON, NKILA, BCALM, GAS5, PVT1), and cell effector functions (IFNG-AS1, TH2-LCR). Here we review lncRNA involvement in adaptive immunity and the implications for autoimmune diseases (multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis) and T/B cell leukaemias and lymphomas (CLL, MCL, DLBCL, T-ALL). It is becoming clear that lncRNAs are important in adaptive immune response and provide new insights into its orchestration.
34948139 1,25-Dihydroxyvitamin D3 and 20-Hydroxyvitamin D3 Upregulate LAIR-1 and Attenuate Collagen 2021 Dec 12 Vitamin D plays a crucial role in regulation of the immune response. However, treatment of autoimmune diseases with 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D3] doses sufficient to be effective is prohibitive due to its calcemic and toxic effects. We use the collagen-induced arthritis (CIA) model to analyze the efficacy of the noncalcemic analog of vitamin D, 20S-hydroxyvitamin D3 [20S(OH)D3], as well as 1,25(OH)(2)D3, to attenuate arthritis and explore a potential mechanism of action. Mice fed a diet deficient in vitamin D developed a more severe arthritis characterized by enhanced secretion of T cell inflammatory cytokines, compared to mice fed a normal diet. The T cell inflammatory cytokines were effectively suppressed, however, by culture of the cells with 20S(OH)D3. Interestingly, one of the consequences of culture with 1,25(OH)(2)D3 or 20S(OH)D3, was upregulation of the natural inhibitory receptor leukocyte associated immunoglobulin-like receptor-1 (LAIR-1 or CD305). Polyclonal antibodies which activate LAIR-1 were also capable of attenuating arthritis. Moreover, oral therapy with active forms of vitamin D suppressed arthritis in LAIR-1 sufficient DR1 mice, but were ineffective in LAIR-1(-/-) deficient mice. Taken together, these data show that the effect of vitamin D on inflammation is at least, in part, mediated by LAIR-1 and that non-calcemic 20S(OH)D3 may be a promising therapeutic agent for the treatment of autoimmune diseases such as Rheumatoid Arthritis.
34811438 Loss of mutual protection between human osteoclasts and chondrocytes in damaged joints ini 2021 Nov 22 Osteoclasts are multinucleated, bone-resorbing cells. However, they also digest cartilage during skeletal maintenance, development and in degradative conditions including osteoarthritis, rheumatoid arthritis and primary bone sarcoma. This study explores the mechanisms behind the osteoclast-cartilage interaction. Human osteoclasts differentiated on acellular human cartilage expressed osteoclast marker genes (e.g. CTSK, MMP9) and proteins (TRAP, VNR), visibly damaged the cartilage surface and released glycosaminoglycan in a contact-dependent manner. Direct co-culture with chondrocytes during differentiation increased large osteoclast formation (p < 0.0001) except when co-cultured on dentine, when osteoclast formation was inhibited (p = 0.0002). Osteoclasts cultured on dentine inhibited basal cartilage degradation (p = 0.012). RNA-seq identified MMP8 overexpression in osteoclasts differentiated on cartilage versus dentine (8.89-fold, p = 0.0133), while MMP9 was the most highly expressed MMP. Both MMP8 and MMP9 were produced by osteoclasts in osteosarcoma tissue. This study suggests that bone-resident osteoclasts and chondrocytes exert mutually protective effects on their 'native' tissue. However, when osteoclasts contact non-native cartilage they cause degradation via MMPs. Understanding the role of osteoclasts in cartilage maintenance and degradation might identify new therapeutic approaches for pathologies characterized by cartilage degeneration.
33933108 Trajectories of disease courses in the inception cohort of newly diagnosed patients with J 2021 May 1 OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory joint disorders with a chronic-remitting disease course. Treat-to-target approaches have been proposed but monitoring disease activity and predicting the response to treatment remains challenging. METHODS: We analyzed biomarkers and their relationship to outcome within the first year after JIA diagnosis in the German Inception Cohort of Newly diagnosed patients with JIA (ICON-JIA). CRP, CXCL9, CXCL10, CXCL11, erythrocyte sedimentation rate, G-CSF, IL-6, IL-17A, IL-18, MCP-1, MIP-1α, MMP-3, S100A8/A9, S100A12, TNFα, and TWEAK were measured at baseline and 3 months later. RESULTS: Two-hundred-sixty-six JIA patients with active disease at baseline were included, with oligoarthritis and rheumatoid factor-negative polyarthritis representing the most frequent categories (72.9%). Most biomarkers were elevated in JIA compared to healthy pediatric controls. Patients with systemic JIA had higher CRP, S100A8/A9 and S100A12 levels compared to other JIA categories. Baseline levels of TWEAK, G-CSF and IL-18 were lower in oligoarthritis patients with disease extension within 1 year. Increased baseline levels of CRP, S100A8/A9, S100A12 and ESR were associated with the subsequent addition of biologic disease-modifying antirheumatic drugs (DMARDs). Higher baseline ESR, G-CSF, IL-6, IL-17A and TNF levels indicated an increased risk for ongoing disease activity after 12 months. CONCLUSION: Our data demonstrate that elevated baseline levels of CRP, S100A8/A9 and S100A12 as well as increased ESR are associated with the necessity to escalate therapy during the first 12 month of follow-up. Furthermore, biomarkers related to Th17 activation may inform on future disease course in previously treatment-naïve JIA patients.